We demonstrate lasing into counterpropagating modes of a ring cavity using a gas of cold atoms as a gain medium. The laser operates under the usual conditions of magneto-optical trapping with no ...additional fields. We characterize the threshold behavior of the laser and measure the second-order optical coherence. The laser emission exhibits directional bistability, switching randomly between clockwise and counterclockwise modes, and a tunable nonreciprocity is observed as the atoms are displaced along the cavity axis.
We present experiments on ensemble cavity quantum electrodynamics with cold potassium atoms in a high-finesse ring cavity. Potassium-39 atoms are cooled in a two-dimensional magneto-optical trap and ...transferred to a three-dimensional trap which intersects the cavity mode. The apparatus is described in detail and the first observations of strong coupling with potassium atoms are presented. Collective strong coupling of atoms and light is demonstrated via the splitting of the cavity transmission spectrum and the avoided crossing of the normal modes.
Background: It has been reported that KRAS mutations (and to a lesser extent KRAS mutations with the BRAF V600E mutation) negatively affect response to anti-epidermal growth factor receptor (EGFR) ...mAbs in metastatic colorectal cancer (mCRC) patients, while the biological impact of the EGFR pathway represented by PI3K/PTEN/AKT on anti-EGFR treatment is still not clear.
Patients and methods: We analysed formalin-fixed samples from a cohort of 32 mCRC patients treated with cetuximab by means of EGFR immunohistochemistry, EGFR and PTEN FISH analysis, and KRAS, BRAF, PI3KCA, and PTEN genomic sequencing.
Results: Ten (31%) of 32 patients showed a partial response to cetuximab and 22 (69%) did not nonresponder (NR). EGFR immunophenotype and FISH-based gene status did not predict an anti-EGFR mAb response, whereas KRAS mutations (24%) and PI3K pathway activation, by means of PI3KCA mutations (13%) or PTEN mutation (10%)/loss (13%), were significantly restricted to, respectively, 41% and 37% of NRs.
Conclusion: These findings suggested that KRAS mutations and PI3KCA/PTEN deregulation significantly correlate with resistance to cetuximab. In line with this, patients carrying KRAS mutations or with activated PI3K profiles can benefit from targeted treatments only by switching off molecules belonging to the downstream signalling of activated EGFR, such as mammalian target of rapamycin.
Following neoadjuvant chemotherapy for operable gastroesophageal cancer, lymph node metastasis is the only validated prognostic variable; however, within lymph node groups there is still ...heterogeneity with risk of relapse. We hypothesized that gene profiles from neoadjuvant chemotherapy treated resection specimens from gastroesophageal cancer patients can be used to define prognostic risk groups to identify patients at risk for relapse.
The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial (n = 202 with high quality RNA) samples treated with perioperative chemotherapy were profiled for a custom gastric cancer gene panel using the NanoString platform. Genes associated with overall survival (OS) were identified using penalized and standard Cox regression, followed by generation of risk scores and development of a NanoString biomarker assay to stratify patients into risk groups associated with OS. An independent dataset served as a validation cohort.
Regression and clustering analysis of MAGIC patients defined a seven-Gene Signature and two risk groups with different OS hazard ratio (HR) 5.1; P < 0.0001. The median OS of high- and low-risk groups were 10.2 95% confidence interval (CI) of 6.5 and 13.2 months and 80.9 months (CI: 43.0 months and not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (HR 3.6 in node positive group, P = 0.02; HR 3.6 in high-risk group, P = 0.0002), and not prognostic in surgery only patients (n = 118; log rank P = 0.2). A validation cohort independently confirmed these findings.
These results suggest that gene-based risk groups can independently predict prognosis in gastroesophageal cancer patients treated with neoadjuvant chemotherapy. This signature and associated assay may help risk stratify these patients for post-surgery chemotherapy in future perioperative chemotherapy-based clinical trials.
We discuss the prospects for enhancing absorption and scattering of light from a weakly coupled atom in a high-finesse optical cavity by adding a medium with large, positive group index of ...refraction. The slow-light effect is known to narrow the cavity transmission spectrum and increase the photon lifetime, but the quality factor of the cavity may not be increased in a metrologically useful sense. Specifically, detection of the weakly coupled atom through either cavity ringdown measurements or the Purcell effect fails to improve with the addition of material slow light. A single-atom model of the dispersive medium helps elucidate why this is the case.
Patients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic ...approaches but lack of chronological references makes dating the exact onset of tumours very challenging.
Here, we describe the case of a colorectal cancer (CRC) patient presenting with synchronous lung metastasis and metachronous thyroid, chest wall and urinary tract metastases over the course of 5 years. The chest wall metastasis was caused by needle tract seeding, implying a known time of onset. Using whole genome sequencing data from primary and metastatic sites we inferred the complete chronology of the cancer by exploiting the time of needle tract seeding as an in vivo ‘stopwatch’. This approach allowed us to follow the progression of the disease back in time, dating each ancestral node of the phylogenetic tree in the past history of the tumour. We used a Bayesian phylogenomic approach, which accounts for possible dynamic changes in mutational rate, to reconstruct the phylogenetic tree and effectively ‘carbon date’ the malignant progression.
The primary colon cancer emerged between 5 and 8 years before the clinical diagnosis. The primary tumour metastasized to the lung and the thyroid within a year from its onset. The thyroid lesion presented as a tumour-to-tumour deposit within a benign Hurthle adenoma. Despite rapid metastatic progression from the primary tumour, the patient showed an indolent disease course. Primary cancer and metastases were microsatellite stable and displayed low chromosomal instability. Neo-antigen analysis suggested minimal immunogenicity.
Our data provide the first in vivo experimental evidence documenting the timing of metastatic progression in CRC and suggest that genomic instability might be more important than the metastatic potential of the primary cancer in dictating CRC fate.
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